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37 Years of Research, Education & Support
Insights From The Kalydeco Journey:
A Real Life Story of Progress and Possibility
By Siri Vaeth-Dunn
Eric Olson, Ph.D.
I
n one of the most anticipated presentations of the 2012 National CF Family
Education Conference, Dr. Eric Olson
(Ph.D.), Vice President and Leader of
the Cystic Fibrosis Franchise at Vertex
Pharmaceuticals, and Dr. Michael Boyle
(M.D.), Director of the Johns Hopkins
Adult CF Center, shared their unique
perspectives on the exciting journey that
led to the Food and Drug Administration’s
(FDA) recent approval of Kalydeco for
use by cystic fibrosis (CF) patients with
the G551D mutation. For many of these
patients, who comprise approximately
4% of the CF population, Kalydeco (also
referred to as VX-770 or Ivacaftor) has had
a dramatic impact on their health and sense
of well-being. For the 96% of people with
CF who have other mutations, the science
behind Kalydeco will lead to the development of new therapies that are showing
promising results in clinical trials.
“I’m going to walk you through a
story,” said Dr. Olson, as he opened his
fascinating presentation, “The Science of
Possibility: Building on More Than 30
Years of CF Research to Discover and
Develop Innovative CF Therapies.” When
telling a story, he explained, “Wherever you
start, you leave out much that came before.”
His prologue included Dr. Paul Quinton’s
pivotal research from 1983 that led to
a new understanding of the role of the
sodium chloride channel in cystic fibrosis.
(continued on page 12)
RESEARCH
A Role for CFTR in Bacterial Killing by the Airways
By Horst Fischer, Ph.D.
CF is caused by a defect in the CFTR
gene. When CFTR was cloned more than
20 years ago, it was immediately noticed
that it forms a chloride channel in epithelial cells. However, the relation between
the defective CFTR and CF lung disease
remained elusive. The major function
of the airways is to filter particles and
microbes out of the airstream so that the
lung remains clean and uninfected. The
normal lung has an arsenal of antimicrobial factors that quickly and efficiently
kill microbes. In CF, this critical function
is impaired, which almost always leads to
colonization of the lung with microbes and
to persistent lung infections.
Because the only difference between a
normal lung and the young, uninfected CF
lung is the CFTR defect, it was reasonable
to assume that CFTR has a role in bacterial defense, which would be defective
in CF. Several years ago, we found that
CFTR is also a channel for bicarbonate.
Bicarbonate is an important pH buffer in
the body and we proposed that CFTR’s
function as a bicarbonate channel would
alkalinize the airway surface liquid. This
was consistent with the finding of clinical
studies that the airway pH was more acidic
in CF than in normal subjects. However,
the finding of an acidic airway surface
(continued on page 22)
Horst Fischer, Ph.D.
Fall 2012
CFRInews™
2012 Fall Issue
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CFRInews™ and the author.
Editorial Chief
Carroll Jenkins
Contributing Editors
Siri Vaeth-Dunn
Bridget Barnes
Contributing Writers
Bridget Barnes
Kristina Benson
Linda Burks
Robert Cumming
JoAnn Davis
Maria Fioccola
Horst Fischer
Kevin Lin
Rod Spadinger
Anabel Stenzel
Laura Tillman
Siri Vaeth-Dunn
Newsletter Staff
Mary Convento
David Soohoo
Graphic Design
Kathy Mitchell
Photography
Craig Burleigh
Tony Patti
Eric Marten
Robert Wright
Audio/Visual
Scott Wakefield
Eric Marten
Randy Evans
Accounting/Bookkeeping
Ann Jones
Elvira Manuel
Board of Directors
Bill Hult, President
Jessica Martens, Vice-Pres.
Anabel Stenzel, Secretary
Ann Jones, Treasurer
Bridget Barnes
Brad Baugh, J.D.
Mike Roanhaus
Kristin Shelton
Siri Vaeth-Dunn
Executive Director
Carroll Jenkins
Director of Programs & Operations
David Soohoo
Development Manager
JoAnn Davis
Program Associate
Mary Convento
Notes from our Executive Director – Fall 2012
It has been an
exciting summer
at CFRI! Our 25th
annual National
Cystic Fibrosis (CF)
Family Education
Conference saw a
continued increase
in attendance, as
acclaimed speakers
addressed a variety
of CF issues. A
review of the CF
Therapeutic Pipeline by Felix Ratjen, M.D.,
gave us a context for specific therapies and
drugs that were presented at this event. New
information on the recently approved Kalydeco
opened up exciting discussions about more
possible discoveries in the near future.
At the same time, the message was clear for
patients: whether you are eligible for Kalydeco
now or for a new product in the future, do not
abandon your ongoing therapies. No drug to
date repairs past damage caused by CF, and
keeping the body as healthy as possible will
maximize the opportunity for good outcomes
as new drugs become available.
Many of the Conference presentations are
reviewed in this issue, and DVDs of different
sessions can be ordered from CFRI. The talk
given on Kalydeco by Eric Olsen, Ph.D., and
Michael Boyle, M.D., and the “Ask the Experts”
panel were broadcast, and can be viewed on our
website http://www.CFRI.org/resources.shtml
under CFRIlive™.
Your generous contributions enable us to fund
top-quality CF research, vetting new projects that
can then go on to the next phase of development.
On page 1, Horst Fischer, Ph.D., describes his
current research at the University of California,
Berkeley. Research at this level leads to breakthroughs in scientific understanding, which in
turn lead to improved treatments for CF.
As we move into an era where there are more
adults than children with CF, we cheer those
who stretch their limits at the USA Transplant
Games. Anabel Stenzel gives us a window
into that event, held this year in Grand Rapids,
Michigan. See p. 17.
The CFRI “2012 RetrEAT: Nourishment for
the Soul” was a wonderful gathering of those
living with CF, who came together on the beautiful Vallombrosa campus. Exercise, arts and
crafts, boating, educational presentations, and
rap sessions contributed to a rich experience.
To share in the “good feeling” of this unique
week, go to: http://youtube/1XkkXKhv8Ls.
Many donors participated in our CFRI
Golf Tournament at the renowned California
top 100 course, Pasatiempo, in Santa Cruz.
Thanks to Scott Hoyt and his committee,
the players had a great time on the greens,
and also enjoyed a fabulous auction and
delicious dinner.
Thank you to our volunteers, who participate
at all levels to help us create these top-quality
events. This year we were joined by a special
intern, Kevin Lin, who shares his impressions
of his experience at CFRI on page 14.
We are all grateful to our sponsors for
supporting the events we offer. They make
it possible for us to keep registration costs low
so that those who need the information and the
community resources are able to attend. Mark
your calendars with the dates noted below!
Finally, keep your eyes open for CFRI’s
new look in the new year. With the help of
Kriss Benson, a graphic designer and CFRI
volunteer, we are updating our logo, and
working to present a more consistent “face”
to our community. We are excited to begin
this process in January, 2013.
Warm wishes,
Carroll Jenkins
Save the Dates
CFRI Teen and Adult Retreat
June 23 – 30, 2013
Vallombrosa Center
Menlo Park, CA
CFRI 26th National
CF Family Education
Conference
August 2 – 4, 2013
Sofitel San Francisco Bay
Redwood City, CA
CFRI Golf Tournament
August 5, 2013
Pasatiempo Golf Club
Santa Cruz, CA
Fall 2012
One Puzzle, Many Pieces: Fitting Together
Multiple Approaches for Best Outcomes in CF
I
By Bridget Barnes
“
’ve spent more of my life caring about
CF than I haven’t,” Dr. Felix Ratjen
revealed in his morning presentation,
“Solving CF Puzzles: New Drugs in the
Pipeline.” As Division Chief of Pediatric
Respiratory Medicine at The Hospital
for Sick Children in Toronto, Canada,
Dr. Ratjen emphasized that there are many
pieces needed to solve the CF puzzle, and
“no one piece fixes the problem but rather,
all the pieces fitting together.” To help
understand the “puzzle pieces” leading to
good outcomes in CF care, Dr. Ratjen
outlined the various means to achieve
that end.
Acknowledging that the lungs are the primary location of disease in cystic fibrosis
patients, Dr. Ratjen spoke about the many
treatment strategies that have been developed over the years, vastly improving
survival rates for people with CF. Reviewing how lung disease develops in CF,
Dr. Ratjen said, “the flux of salt influences
the flux of water, and they need to be in
the right balance to break up the mucus
and stop infection.” He also touched
on the standard treatment strategies
currently used for CF, which have
dramatically improved outcomes for CF
patients. The list of drugs that are currently
being studied or have been approved was
graphically depicted on the Cystic Fibrosis
Foundation’s “Therapeutics Pipeline.”
Dr. Ratjen described how CF drugs are
divided into different categories such as
gene therapy, CFTR modulation, restoring
airway surface hydration, mucus alteration, anti-inflammatory, anti-infective,
and transplantation and nutrition, each
targeting a specific piece of the CF puzzle.
Noting that “good nutrition is key to survival in cystic fibrosis,” Dr. Ratjen added,
“the high-fat diet we use today came from
Toronto.” In a 1988 study that compared
the Toronto CF center, which used a highfat diet, with the Boston center, which
used a low-fat diet, patients in the Toronto
group on average weighed 6 pounds more
and lived nine years longer than their
Boston counterparts. In Canada in 2007,
there were more adult patients with CF
than children. Dr. Ratjen pointed out that,
“Canada has done well over time and has
more adults than pediatric patients due to
aggressive disease management.” Overall
lung function has improved in patients and
the median FEV1 predicted for a 30-yearold patient in Canada was almost 80% in
2007. “It is better than it has been, but not
at a point to stop,” Dr. Ratjen explained.
“We want to do better in the future.”
New targets of therapy and their potential impact are also being studied and
implemented. Hydration therapy with
agents such as hypertonic saline is now a
mainstay in CF care and a “simpler way”
to clear accumulated mucus and prevent
infection. Gene therapy will take longer
to develop as there is currently no major
gene therapy trial going on in the US, and
only one in the UK, where the results have
been “so-so.” According to Dr. Ratjen,
we “won’t see much development of gene
therapy in coming years.”
While it may be years before gene therapy
is available, treating the defect itself
currently offers another very promising
approach to transporting the CFTR protein
to the surface of the cell. In CF there can
be one of two different problems with the
“ion pump” that moves the CFTR protein.
Either the ion pump is not present, or the
ion pump is there, but does not function
properly. The way to fix the problem is:
1) get the pump to where it needs to be
on the surface of the cell, known as a
“corrector;” 2) make the pump perform
better, a “potentiator;” or 3) create an
alternative pump which works on other
ion channels. With the recent approval
of Kalydeco (VX-770), a “potentiator,”
and three other drugs that target the basic
defect in CF currently in trials, Dr. Ratjen
said there are “very exciting possibilities”
in store. He also noted it is important to
learn from what has not worked, such as
denufosol. “Denufosol has a short halflife lasting approximately 50 minutes, so
the study results may have been affected.
With Kalydeco, we saw a huge initial
Felix Ratjen, M.D., F.R.C.P.
bump-up in lung function, very different
from denufusol.”
With regards to drug development in
cystic fibrosis, Dr. Ratjen focused on
hypertonic saline and bronchitol as
examples of hydration therapy in CF.
“Cilia transports mucus, and the airways
need enough fluid so the cilia can ‘wave.’”
Coincidentally, the solution to this problem
was found on a wave. Australian surfers with CF found that saltwater helped
clear clogged mucus, leading to better
lung function and the development of
hypertonic saline. Bronchitol (or inhaled
mannitol), is a sugar that draws water to
the airways, which is delivered as a dry
powder and requires no nebulizer. A study
of CF patients using bronchitol showed a
7% increase in lung function, and it is now
available to adult patients in Europe.
Airway infection in cystic fibrosis caused
by pathogens specific to the disease is a
chronic concern. “Staph aureus is the
most common bug, not pseudomonas,”
according to Dr. Ratjen. “It’s changed
because we have been more aggressive
on pseudomonas than Staph.” He added,
“Prevention of chronic infection has
become paramount and is a major treatment target.” To combat pseudomonas,
several studies compared intravenous to
inhaled therapies. As an anti-infective,
inhaled tobramycin (TOBI) is considered
the standard of care to date. It achieves high
(continued on page 22)
Fall 2012
Antioxidants, Probiotics and Vitamins:
The Vital Importance of Nutrition and Screening
A
By Siri Vaeth-Dunn
nyone who has glanced at a
health or fitness magazine lately
has likely seen references to
antioxidants, probiotics and vitamins.
While beneficial for most people, they
can be especially crucial for those with
cystic fibrosis (CF). In her enlightening
presentation, “Nutrition Essentials for
CF: Antioxidants, Vitamin D and More,”
Terri Schindler, M.S., a registered dietitian at the CF Center at Rainbow Babies
and Children’s Hospital in Cleveland
Ohio, shared valuable information about
nutrition and its impact on those with CF.
As presented by Schindler, antioxidants are “substances that are capable
of counteracting damaging effects of
oxidation in tissues, as they neutralize
free radicals,” which are believed to lead
to cellular damage. Key antioxidants
include vitamin E, C, Beta-carotene
and selenium. Studies on the impact of
antioxidant supplementation on lung
disease and pulmonary exacerbations
have had conflicting results. While some
researchers have found that patients
with CF using antioxidant supplements
had a reduction in CF-related pulmonary exacerbations, others found that
antioxidant supplementation “caused
no harm…but showed no benefit.”
Schindler emphasized that in addition to
oral supplements, people should strive
to eat foods that are high in antioxidant
micronutrients.
Vitamin D has long been recognized
as a key component to optimal bone
health, as it assists in the absorption
of calcium and phosphorus. Schindler
cited a study which clearly indicated the
inverse relationship between vitamin D
levels and bone fractures. Vitamin D has
been found to reduce the risk of falls in
post-menopausal women by nearly 50%,
and leads to significant improvement in
neuromuscular function in the elderly. In
light of the increased risk of osteopenia
and osteoporosis for those with CF due to
poor nutrient absorption, the importance
of adequate vitamin D levelsis paramount.
In addition to bone health, Schindler noted
that vitamin D supplementation is associated with a “significant reduction in the
risk of influenza and the common cold.”
A recent study suggested that vitamin
D might also serve as an effective antiinflammatory. Common sources of vitamin
D include ergocalciferol (D2), which is
available by prescription, cholecalciferol
(D3), which is “what we make in our skin
from exposure to UV-B light,” and what
Terri Schinder, M.S., R.D.
is commonly found in over-the-counter
supplements and sunlight. Noted Schindler,
“the body can synthesize vitamin D from
only ten to fifteen minutes of sunlight on
the arms and legs without sunscreen.” The
Cystic Fibrosis Foundation (CFF) recently
published new guidelines for vitamin D,
suggesting that levels should be checked
near the end of winter, when levels are usually lowest. The CFF recommended the use
of D3 (cholecalciferol) instead of D2
(ergocalciferol), with the goal of “a minimal 25-hydroxyvitamin D concentration of
30 ng/ml (75 nmol/liter)” for those with CF.
Schindler discussed the possible benefits
of probiotics for those with CF, as the
antibiotics commonly prescribed to them
often wreak havoc with the beneficial bacteria and flora in the intestinal tract. The
introduction of probiotics, “live micro-
organisms, which when administered in
adequate amounts, confer a health benefit
on the host,” may be helpful in addressing antibiotic-associated diarrhea. A small
study of 10 CF patients who were treated
for six months with probiotic supplementation – specifically, lactobacillus GG
– found a significant reduction in pulmonary exacerbations, though there was no
notable difference in pulmonary function
levels or inflammatory markers. Schindler
stressed that patients should confer with
their doctors prior to taking probiotics.
It is important to “pick a product from
a trusted manufacturer and to choose a
product with the right quantity of colony
forming units.” Probiotics may be dangerous for those people who have had lung
transplants and it is especially critical that
they consult with their doctors prior to use.
Schindler discussed several “hot topics” in
CF nutrition, including the use of growth
hormones, insulin therapy, and vitamin
K. The height of many children with CF
is impacted due to impaired nutritional
absorption. A multi-center clinical trial of
growth hormone treatment for children
with CF found that use of the growth
hormone rhGH improved growth, lean
body mass, and lung function. Schindler
addressed the benefits of slow-release
insulin therapy for those people with CF
who have impaired glucose tolerance.
A three-year study in which CF patients
with insulinopenia (a deficiency of insulin
secreted by the pancreas) were treated
with low-dose insulin found that this
therapy helped to prevent lung function
decline. Vitamin K, a fat-soluble vitamin
which assists with blood clot formation
and bone health, is commonly prescribed
as part of the CF care regimen. Vitamin
K deficiency is linked to hemoptysis
(bleeding in the lungs or bronchial tubes).
Schindler stressed that vitamin K is “often
not found in over-the-counter vitamin
supplements, and that it has a history of
being under-dosed.”
Other “hot topics” include the prevention
(continued on page 23)
Fall 2012
Partnership Provides Best Care for Adults with CF
W
By Bridget Barnes
hat are the top ten adult Cystic
Fibrosis (CF) Centers in the
United States doing to achieve
the best health outcomes for their patients?
In his engaging talk, “Providing the Best
Care for Adults with CF: A Partnership
with Patients and Families,” Dr. Michael
Boyle presented a very clear set of guidelines based on information he gathered
in his study. Among his many duties as
Director of the Adult Cystic Fibrosis
Program and Assistant Professor of
Medicine at the Johns Hopkins Medical Institutions in Baltimore, Dr. Boyle
led the Adult CF Quality Improvement
project inspired by “the idea of how we as
caregivers, patients, and families can work
together to get the best outcomes.” He
visited each of the ten centers to learn how
they deliver their care and distilled the
best common practices employed by each.
The following questions served as the
basic criteria for discovering what leads to
better health for adults with CF: 1) Does
what we do as caregivers, patients and
families make a difference in the severity of CF, or is the course determined by
genetics? 2) How can we create a partnership between caregivers and patients to
assure the best possible care? 3) What are
the strategies to help young people with
CF become successful adults with CF?
As to whether or not severity of lung
disease in CF is attributable solely to
genetics, or whether other factors play a
role, Dr. Boyle reported, “When looking
at identical twins, their FEV1 was similar
when living at home together, but after
living apart there was four times more
variability.” Showing a slide with a mother
holding an apple pie, Dr. Boyle jokingly
concluded, “The recipe for a good outcome is to provide everyone with a mom.”
Today, when more than half of the
people living with cystic fibrosis are
adults, Dr. Boyle cited examples of adults
who take responsibility for themselves
and added, “It’s actually healthier for this
age group with CF to have inspirational
peers in their lives than a doting mom.”
In a study at Johns Hopkins that followed
the clinical and pharmacy records of 95
CF patients for twelve months, Dr. Boyle
Michael Boyle, M.D.
reported, “patients do better if they take
their medications and have them available
in their medicine cabinets.” The study
showed, “If 80% of one’s medications
were being filled, there were no exacerbations. If medications were only being
filled 40 to 60% of the time, exacerbations
increased,” demonstrating that compliance
is crucial.
Partnering with caregivers is also a vital
component in ensuring that adults with
(continued on page 18)
An Adult’s Perspective on “Providing the Best
Care for Adults with CF”
A
By Kristina Benson
s an adult with cystic fibrosis
(CF), I was very interested in
hearing Dr. Boyle’s presentation
on adult care. Dr. Boyle suggested starting
the transition to adult disease management with small steps, at an early age. I
thought it was insightful to suggest setting
goals regularly, in order to gradually give
teens with CF time to develop a sense of
responsibility. From my experience, while
parental guidance is essential, parents must
not do everything for their teen as he or
she approaches adulthood.
I found it refreshing that Dr. Boyle
addressed the need for a partnership
between adults with CF and their clinic.
He discussed how his clinic staff prepares
for each patient’s visit; and he advised
CF adults to prepare for upcoming appointments with questions and observations. His
clinic helps CF adults to understand their
own personal data like FEV1, weight/BMI,
microbiology, key labs, and radiology. Dr.
Boyle then stressed the importance of exit
paperwork that establishes individualized
goals between clinic visits.
I appreciated the idea of greater transparency for adults with CF, and I liked the
“picture interventions” used by his center
to show patients what is happening to their
lungs in a CT or x-ray. These illustrate
the need for good self-care and provide
motivation. I think creative thinking like
this is encouraging.
Dr. Boyle mentioned the fine line that an
adult CF doctor walks: he must be nice, but
not too nice. He believes in aggressive and
proactive treatment, and in not allowing
long stretches without clinic visits. And he
recommended that CF adult care needs to
be individualized, acknowledging the varying reasons for noncompliance including
finances, depression /anxiety, embarrassment, and life events.
Dr. Boyle’s talk addressed many of the
unique needs of adults living and thriving
with CF. I encourage those who missed the
conference to order the DVD from CFRI.
Fall 2012
A New Perspective on CF Care
Presented at Annual Conference
I
By Bridget Barnes
n order to convey the dramatic
improvements that have taken place
in cystic fibrosis (CF) care over the
past 30-plus years, Dr. Karen Hardy,
Director of Bay Area Pediatric Pulmonary at Children’s Hospital Oakland and
California Pacific Medical Center in San
Francisco, shared stories about her early
days as an intern. Asked by Isabel StenzelByrnes to do “CF 201,” Dr. Hardy, with no
notes in hand, gave an insightful and comparative analysis of how the treatment of
CF has changed over the years during her
presentation entitled, “CF Care: Getting
A New Perspective.”
Dr. Hardy’s first patient was a 17-year-old
girl with cystic fibrosis on oxygen full
time “who touched my heart.” According
to Dr. Hardy, “she wanted to know my age
and if I was good with IVs. When I said
‘Yes,’ she said, ‘Good, I only have one
vein left.’ Her goal was to survive to her
18th birthday.” It was this fateful meeting that led Dr. Hardy to pursue a career
specializing in CF clinical care. She completed her fellowship in 1986 in Pediatric
Pulmonary Disease and Cystic Fibrosis at
Saint Christopher’s Hospital for Children
in Philadelphia, which had 400 patients.
She recounted how Dr. Stan Field, one of
her mentors, was also there to learn about
pediatric patients, as he was beginning to
consider transition at that time. His influence made Dr. Hardy a big proponent of
transition as she recognized that children
need to “graduate” and move forward to
an adult center. This idea was one of the
many precursors that changed the way CF
care is imagined and delivered today.
In 1989 the CFTR gene was discovered. “It
was a very exciting year and everyone was
optimistic thinking that within a decade
we’ll have a cure,” Dr. Hardy recounted.
“But we didn’t.” In the meantime, big
advances were made in mucus alteration with the development of Pulmozyme
and anti-infectives such as Azithromycin
and TOBI. Hypertonic saline was also
approved and made available to patients
with CF as a way to improve airway
Karen Hardy, M.D.
surface liquid. All of these therapies
improved lung function.
In describing the ways in which treatments
have changed over the years, Dr. Hardy
noted, “CF has truly changed from a fatal
illness to a chronic disease.” As more
medications have been discovered, the
focus has been on merging therapies in
an effort to reduce treatment time without
compromising the benefits. Dr. Hardy used
the example of nebulizers for bronchodilation,
which “are not necessary anymore,” as MDI’s
(metered dose inhalers) are quicker, just as
effective and far more portable.
There are multiple ways of clearing mucus
from the lungs including autogenic drainage, active cycle of breathing, using a
vest, PEP or flutter, as well as a number
CFRI’s 25th National CF Family Education Conference
of aerosol treatments. Dr. Hardy clarified the order in which aerosol treatments
have been found to be most effective.
“Start with a bronchodilator or metered
dose inhaler (MDI) to open up airways,
then breathe in hypertonic saline, which
adds fluid and moves mucus, and finally
Pulmozyme, which chops up the rafts of
mucus.” She also explained that adding
PEP or flutter to vest therapy, “helps keep
airways open that have grown floppy with
age.” Non-medical treatments such as
trampoline, pogo stick, all wind instruments, running, swimming, horseback
riding, or any sport with high impact are
also very beneficial.
Saving the best for last, Dr. Hardy talked
about Kalydeco, “the exciting new Vertex
product,” which targets the basic defect in
cystic fibrosis and restores ion transport
to the cell surface. A couple of patients in
her clinic with the G551D mutation are
using the new drug and according to Dr.
Hardy, “the results have been amazing,
and patients may be able to decrease
other treatments.” She concluded her
talk by joking that she was “the opening
act for Paul Quinton, who we’re all here
to see,” and enthusiastically noted once
again how dramatically different and
positive the CF treatment landscape has
become. Dr. Hardy won CFRI’s Professional of the Year Award in 2011, and
was Best Bay Area Doctor in 2009.
Fall 2012
Dr. Paul Quinton:
Inspiring CF Researcher and Role Model
F
By Rod Spadinger
their impermeability to chloride. As such,
the chloride could not get out across the
duct, could not be reabsorbed back into
the blood, and wound up on the surface
of the skin. This is the basis for the thick
and sticky mucus that permeates the
bodies of CF patients.
or many years, it was generally
assumed that those diagnosed with
cystic fibrosis (CF) would live a
brief and relatively unproductive life.
Several decades ago, that may have
been accepted as truth. However,
Dr. Paul Quinton, who spoke at the
25th National CF Family Education
Conference, defies the odds each and
every day. As we learned during his presentation, “Kicking Butt With CF at 67!”
Dr. Quinton’s life is the extreme opposite
of brief and unproductive.
Dr. Quinton, currently a professor of
Biomedical Science at the University of
California, San Diego, was born in 1944,
a time when cystic fibrosis was largely
unknown by the medical community.
While in the fifth grade, Dr. Quinton
failed a school Tuberculosis test and
it was discovered that something was
wrong with his lungs. As a result of the
relative obscurity of CF, he was not
diagnosed with cystic fibrosis until the
age of 19 years. Until that point, it was
assumed that he merely had stubborn
respiratory infections that could not be
properly treated. Dr. Quinton’s first
diagnosis was that of chronic bronchitis.
While a sophomore at the University of
Texas, Dr. Quinton read literature that led
him to a self-diagnosis of cystic fibrosis.
T
Paul Quinton, Ph.D.
It was then that he was introduced to Dr.
Gunyon Harrison of Baylor University, his
first physician who was a specialist in the
treatment of CF patients. Dr. Harrison was
able to medically confirm through a series
of sweat tests that Dr. Quinton did, indeed,
have cystic fibrosis.
Early in Dr. Quinton’s career, while
working at the University of California,
Riverside, he analyzed the sweat ducts of
CF patients, and with the assistance of his
colleagues, was able to discover an abnormality in these ducts. The team concluded
that the problem with the ducts was due to
During his presentation, Dr. Quinton
shared some personal moments about
his life as a CF patient. He divulged that
when he was first diagnosed with cystic
fibrosis, he chose to keep the discovery
largely to himself, informing just a few
people about his condition. It was only
when his experience with CF appeared in
the San Jose Mercury newspaper, that he
was able to freely disclose his situation.
Dr. Quinton concluded his presentation
with thoughts about how he felt about
death, and whether he is fearful. He
remarked that to him, death is inspirational: it drives us to live. Further, it is
his view that the challenge of death
can inspire people to be more than they
otherwise would.
The rich and full life that Dr. Quinton
leads provides an example to all living
with cystic fibrosis that being diagnosed
with CF is not the beginning to an end.
Rather, it is merely a beginning with
boundless possibility.
Reflections on My First CFRI Conference
By Maria Fioccola
he 25th Anniversary of the
National Cystic Fibrosis Family
Education Conference was held at
the Sofitel San Francisco Bay, in Redwood
City, California. This year’s theme was
“Facing CF Together with Confidence.”
I traveled from Chicago to attend the
conference for the first time.
You may wonder how I got involved from
so far away. An adult with cystic fibrosis
(CF), I am on the Board of Directors for
USACFA (United States Adult Cystic
Fibrosis Association) and Secretary for
the Northwestern University Patient
Advisory Board. I learned about the CFRI
conference through fellow board members who have attended in the past. I was
honored to be asked to attend on behalf of
USACFA, but needed help with expenses.
Fortunately, I received a scholarship from
CFRI, USACFA helped with my airfare,
and the Sofitel offered CFRI Conference
attendees a discounted room rate. With
the essentials taken care of, I was ready to
book my trip!
I was nervous at the thought of traveling
alone and visiting a new city and I was grateful for the patience and help from the CFRI
staff! Upon arriving in San Francisco, I was
greeted by Mary Convento, who drove me to
(continued on page 23)
Fall 2012
Exploring Your Options:
Effective Airway Clearance Treatments
A
By Linda Burks
can tolerate a 7% saline solution, but do
not significantly benefit from it. irway clearance is the neverending, time-consuming, lifesustaining ritual practiced in
every cystic fibrosis (CF) household.
We constantly wonder about it. “Am I
doing the best I can?” “Should I be doing
anything differently?” “Is airway clearance really worth the time and effort?”
Mary Lester, a Registered Respiratory
Therapist at the Medical University of
South Carolina (MUSC) in Charleston,
directly addressed these concerns during
her presentation, “Effective Airway
Clearance Treatments.”
Lester advocates that airway clearance
is for everyone. Since no airway clearance method has proven to be superior to
others, respiratory therapists must help
patients decide which method will work
well for them. Lester informs her patients
about all the options, listens to patient
opinions, and then works with individuals to determine which method is best for
them. Some factors she considers when
selecting airway clearance techniques are
the patient’s motivation, the patient’s goal,
the caregiver’s goal, effectiveness, patient
age, and ease of learning and teaching. With twelve years experience as the lead
respiratory therapist at MUSC, Lester
emphasized that airway clearance is an
active process. Since it can be rather boring, patients need to figure out how to stay
involved. Illustrating that patients can integrate treatments into an active lifestyle,
Lester described the routine of a particularly creative patient. This motivated CF
adult has machines set up in his car so that
Mary Lester, R.R.T., R.C.P.
he can do airway clearance as he drives to
and from work. How does Lester know
his set up works? The patient coughs,
coughs, and coughs some more. The Medical University of South Carolina serves a wide population. Being the
only adult CF center in South Carolina,
MUSC has almost twice as many adult
patients as pediatric ones. With newborn
screening, many CF children are being
diagnosed at birth. While young babies
are consistently given chest physiotherapy
with a bronchodilator, effective airway
clearance techniques typically change for
an individual over time. As with older
patients, it is recommended that infants
begin TOBI at the first positive culture
for Pseudomonas aeruginosa. Hypertonic
saline use is recommended at a later age.
According to the results of a recent study
on the effectiveness of inhaled hypertonic
saline on infants (known as ISIS), infants
“...exercise is
an important
adjunctive
therapy.”
Lester recommends giving “lots of
thought about when to get a device,
because you don’t want it to be put in a
closet.” She does not discuss a high-frequency chest wall compression (HFCWC)
device until after a child turns two. A
HFCWC device is more commonly known
as a “vest,” and there are now three vest
manufacturers to choose from. Since
different types of airway clearance may
be more effective than others at different stages of life, Lester believes patients
should know all of the options for chest
physiotherapy. In addition to HFCWC,
recommended therapies include autogenic
drainage and IPV (intrapulmonary percussive ventilator). Autogenic drainage is
unique in that the patient can perform it
alone and in a sitting position; however,
autogenic drainage requires training and
intense focus and concentration. To help
clear sputum, an IPV delivers shorts bursts
of air into the airways. Nebulized medicine can be administered at the same time.
Once patients are informed about their
airway clearance options, Lester acknowledges that the final decision may still be
based on a “gut feeling.”
Finally, Lester endorses exercise. Consistent research has not shown if exercise
can replace airway clearance techniques.
However, experience shows that exercise
is an important adjunctive therapy. With
exercise, it’s easy to follow Lester’s main
guidelines. Be creative. Be consistent.
And be sure to cough. Fall 2012
Men with CF Are Having Children!
connects the sperm-producing testicles to
the penis.
The good news, as detailed by Dr. Turek,
is that there are well-defined and successful surgical sperm retrieval procedures
for men with CF who are missing the
vas deferens. Choices include retrieving
it from the epididymis, an organ above
the testicle where sperm is stored, or via
testis (testicular) sperm. According to
Dr. Turek, the quality of the sperm is
generally identical, regardless of from
where it is retrieved.
Paul J. Turek, M.D.
A
By Rod Spadinger
mong the category of challenges
that men with cystic fibrosis
(CF) face is the topic of male
reproductive capacity. For many years,
it was assumed that men with CF were
not able to father children due to infertility issues. Over the past few years, however, barriers have been breached with
science, which now allows men with
CF to reproduce. At the 25th National
CF Family Education Conference,
Dr. Paul Turek, infertility specialist and
founder of The Turek Clinic, delivered a
presentation entitled, “Men With CF
Are Having Children!” As detailed by
Dr. Turek, the majority of men with
cystic fibrosis are capable of having children, albeit with the aid of technology.
The primary reason that men with CF
are unable to reproduce naturally is the
result of a tube, called the vas deferens,
which was not properly formed prior to
birth due to complications related to
the Cystic Fibrosis Transmembrane
conductance Regulator (CFTR) protein.
This causes mucus to clog the vas
deferens while it forms, leading to its
deterioration and absence in newborns.
Approximately 99% of men with cystic
fibrosis are missing the vas deferens.
Termed Congenital Absence of the Vas
Deferens (CAVD), this anatomical defect
provides a reproductive roadblock for
men, as the vas deferens is the tube that
The most successful method of retrieving epididymal sperm is through Microsurgical Epididymal Sperm Aspiration
(MESA). In this process, a small incision
is made in the scrotal skin and, aided
by the use of optimal magnification,
tubules of the epididymis are examined
and opened, which allows for the identification and collection of quality sperm.
Percutaneous Epididymal Sperm Aspiration (PESA) does not require an incision.
Instead, a needle penetrates the scrotal
skin and retrieves sperm that is found.
“The good news...
is that there are
well-defined and
successful surgical sperm
retrieval procedures
for men with CF
who are missing
the vas deferens.”
Dr. Turek prefers MESA to PESA because
MESA allows the surgeon to identify and
extract quality sperm tubules, whereas
PESA is a “random” technique that does
not allow the surgeon to be certain that
the extracted sperm are of good quality.
Because of this, MESA typically needs
to be performed only once, while PESA
procedures often need to be repeated.
To a lesser extent, CF male fertility may
also be challenged by very little epididymis to store sperm, or merely low sperm
production. A significant obstacle for
men with CF with low sperm production is that sperm is difficult to find and
subsequently retrieve in the testicle. To
address this, Dr. Turek has developed a
mapping procedure that enables the surgeon to determine whether or not sperm
exist in the testicles. In this instance, the
testicle must be entered surgically, with
the most successful procedure being
Testicular Sperm Extraction (TESE).
With TESE, a small piece of testicular
tissue is removed through an incision in
the skin, allowing for the extraction of
the sperm.
Once sperm is retrieved from the patient,
Intracytoplasmic Sperm Injection (ICSI)
is performed. With this procedure, the
extracted sperm is inserted via a needle
into the cytoplasm, the inner part of a
woman’s egg. ICSI is preferred to in
vitro fertilization, where the sperm is
placed near the egg, because the sperm
retrieved is not mature enough to fertilize
the egg without the directed assistance
that ICSI provides.
Thanks to the enormous efforts and
expertise of physicians such as Dr. Paul
Turek, the possibility of men with CF
having biological children has become
a reality.
Fall 2012
The Trauma of Diagnosis: PTSD and Cystic Fibrosis
W
By Siri Vaeth-Dunn
hen Heather Walter’s daughter
was diagnosed with cystic
fibrosis (CF), the news triggered a wide range of emotions.
During her thought-provoking presentation, “PTSD (Post Traumatic Stress
Disorder): Confronting High Anxiety
with Confidence,” Dr. Walter, a professor
of organizational communication at the
University of Akron, recalled that when
her daughter’s doctor shared the devastating news, he told her that children
with CF were living into their twenties.
Much to Dr. Walter’s shock, this information was “presented like good news.”
Dr. Walter recounted that as she was
“falling into the CF world,” the stress
and disorientation caused her to feel
“defined by the diagnosis.” She likened
her experience to having arrived in a
new country, where she was faced with
a completely unfamiliar language and
culture. She felt, in a word, traumatized.
Heather Walter, Ph.D.
In her search to understand this new CF
world, Dr. Walter employed her academic
research skills and discovered the work
of a Brazilian psychiatrist, Mariana
Cabizuca, from the Institute of Psychiatry at the Federal University of Rio de
Janeiro. Dr. Cabizuca and her associates
conducted a study to assess the preva-
10
lence of post-traumatic stress disorder
(PTSD) among parents of children
with CF. In their article, “The Invisible
Patients: Post Traumatic Stress Disorder
in Parents of Individuals with Cystic
Fibrosis,” the researchers found that 6.5%
of study respondents had “full PTSD,”
while 19.4% of surveyed parents had
“partial PTSD.”
PTSD is an anxiety disorder caused by
exposure to some form of traumatic event
that often involves the threat of injury
or death. Usually associated with those
who have experienced extreme violence,
including rape victims and war veterans,
there is now a growing understanding that
the diagnosis of a life-threatening disease
triggers the same anxiety response.
Typically there are three responses
to PTSD: re-experiencing/re-living,
avoidance, and arousal. People who
“re-experience,” are often faced with
intrusive recollections, nightmares and
flashbacks, and continue to relive the
traumatic events. Situations that remind
people of the original event can cause
strong reactions. In Dr. Cabizuca’s study,
63% of the parents experienced the
re-living of the diagnosis.
Those who respond with “avoidance,”
often feel detached from others. They
avoid anything related to the traumatic
event that may trigger symptoms. People
with avoidance often have a sense of
foreboding about the future, and diminished interest in their usual activities. While
only 11% of people in the Brazilian study
reported this, Dr. Cabizuca hypothesized
that those who are experiencing avoidance
were unlikely to participate in a study and
were therefore likely under-reported.
The third common symptom of PTSD is
“arousal,” a state of hyper-vigilance and
hyper-alertness. People experiencing this
arousal often suffer from insomnia, are
unable to relax, and may have an exaggerated response to anything that startles
them. Of the parents in Dr. Cabizuca’s
study, 63% reported experiencing
this symptom.
How to manage the symptoms of posttraumatic stress disorder? Dr. Cabizuca
recommended that CF care teams ask
parents of patients about their emotional
health and the possibility of psychological/psychiatric treatment. For many,
knowing that they are not alone may
be enough to alleviate the symptoms.
Participation in support groups can be
useful – both online and in-person. The
social worker at the CF Center can provide direct support, or referrals to other
counselors. Behavioral therapy is very
effective for some, as are anti-anxiety
medications.
Dr. Walter shared the personal lessons
she has learned since her daughter’s
diagnosis. First and foremost, “There is
help out there.” She noted the importance
of understanding that some days, “avoidance is not a bad thing.” And due to the
nature of the disease, it is likely that each
new “sub-diagnosis” – for example, new
infections and cystic fibrosis related
diabetes – can trigger the stress of the
initial diagnosis. Most importantly,
symptoms of PTSD should not be ignored.
As Dr. Cabizuca wrote about the parents
in her study, “their suffering remains
‘invisible’ to the medical system, leading
to under-diagnosis and under-treatment.”
To read the article by Dr. Cabizuca
go to: http://www.scielo.br/scielo.
php?pid=S0101-60832010000100002&s
cript=sci_arttext&tlng=en
Fall 2012
Women With CF Are Having Children!
T
By Siri Vaeth-Dunn
he first successful pregnancy and
birth by a woman with cystic
fibrosis (CF) was documented in
1959. At a time when few people with
CF survived early childhood, this was
a remarkable event. As the median life
expectancy for those with CF increases,
as well as their quality of life, more
women with cystic fibrosis are exploring
pregnancy and in 2010, 225 women with
CF delivered babies. In her illuminating
presentation “Women with CF Are Having
Children!” Dr. Lynn Westphal, Associate
Professor of Obstetrics and Gynecology
at Stanford School of Medicine, discussed
the reproductive options currently available to women with CF.
Lynn Westphal, M.D.
Most women with CF are fertile, but
those considering pregnancy will require
additional medical care. According to Dr.
Westphal, the physician’s first step is to
conduct fertility testing with the patient,
including measuring the levels of folliclestimulating hormone (FSH). Should these
tests indicate that fertility is not an issue,
there are other considerations before
proceeding. The woman’s partner must be
tested to assess whether he is a carrier and
the couple should receive genetic counseling. Dr. Westphal stressed that women
should try to reach at least 90% of their
ideal weight, and optimize their health
through adherence to their medical regi-
men. They should also review their medications with their doctor and be screened
early for diabetes. Dr. Westphal emphasized that a successful pregnancy requires
well-coordinated multidisciplinary care.
Most women with cystic fibrosis who are
hoping to bear children will have some
form of procedure utilizing assisted reproductive technology (ART). Most often,
women undergo ovarian stimulation, in
which they are given follicle-stimulating
hormones with the goal of the development of multiple follicles. The next step,
according to Dr. Westphal, is the collection of oocytes (eggs), which are retrieved
using a needle through the top of the
vagina. The eggs are then fertilized.
With traditional in vitro fertilization (IVF),
50,000 to 200,000 sperm are mixed with
the collected eggs. In some cases, intracytoplasmic sperm injection (ICSI) is
utilized, in which a single sperm is directly
injected into each egg.
By the third day, the embryos have 6 to 8
cells, and Dr. Westphal noted that biopsies
of the embryos are usually conducted at
this stage. Pre-implantation genetic diagnosis/screening (PGD/S) involves removing one or two cells from each embryo in
order to test for genetic defects. PGD/S,
said Dr. Westphal, is “well proven for the
diagnosis of a single genetic defect.” The
accuracy of this screening is estimated to
be 85%, and women may choose to have
chorionic villus sampling (CVS) or amniocentesis at a later date for more accurate
results.
Once the embryos have been selected,
they are transferred to the uterus via
catheter, guided by ultrasound. While
IVF implantation often results in multiple
babies, this could have serious implications for women with cystic fibrosis. As
such, Dr. Westphal noted that usually only
one or two embryos are transferred. If the
implantation is successful, “the patient
will be passed to a high-risk obstetrician at
around 10 weeks.”
Women with CF who have undergone
lung transplantation have successfully
had children, but it has additional risks.
Dr. Westphal suggested that women have
a minimum of three years of stable health
post-transplant before considering pregnancy.
She also cautioned that organ rejection is
more frequent during pregnancy.
For those women with CF who are
unable to carry a pregnancy, Dr. Westphal
suggested gestational surrogacy, in which
the woman goes through all the steps of
IVF, but the fertilized embryo is then
transferred to another woman, who will
serve as a surrogate and carry the baby
to term. Noting that California is “surrogate friendly,” Dr. Westphal warned that,
“regulations regarding surrogacy vary by
state and country.”
Much progress has been made in cystic
fibrosis care, with expanded life expectancy and improved quality of life. A
tangible measure of this progress is the
number of women with cystic fibrosis who
– regardless of how they achieve it – have
successfully become mothers.
The CF
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of highly relevant CF topics
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11
Fall 2012
KALYDECO (continued from page 1)
“Most enzymes block
or stop a protein from
doing its function.
We were trying to
make the protein come
to life and function.”
770 development team was formed and
transferred to Cambridge, Massachusetts.
Chapter One began with the question,
“Is it possible to find drugs or therapies
or small molecules that could restore the
function of the CFTR (cystic fibrosis
transmembrane conductance regulator)
protein?” The discovery of the CFTR gene
in 1989 led to focused work on understanding how the CFTR protein worked,
and why various mutations led to “a
misfunction or disfunction” of the sodium
chloride channel. “Understanding the gene
was one thing,” Dr. Olson said,
“also important was identifying the
mutations and clinical phenotypes that
they manifested.”
The G551D mutation is a “class III”
mutation, in which the CFTR protein has
been made and is sitting at the epithelial
surface, but the channel will not open.
As such, this mutation has the greatest potential for research success. As
Dr. Boyle explained succinctly in his
later presentation, “Kalydeco binds to
CFTR…and opens the gate more frequently, with more chloride conductance.
Ivacaftor (Kalydeco) is a potentiator that
increases CFTR channel opening time.”
In the “discovery phase,” as described
by Dr. Olson, researchers cultured airway epithelial cells from autopsies and
transplant patients. Airway cilia in those
with CF are immobilized by mucous and
unable to sweep away particles and bacteria, leading to a cycle of inflammation
and infection. When the cilia of G551D
lung cells were treated with VX-770 in
the lab, they began to move. The moving
cilia showed the potential of VX-770
to repair the “gating” problem with the
channel, and soon after, Vertex conducted a phase 1 clinical trial in healthy
people to determine safety and dosing.
Fortunately, new methodologies were
being developed for high throughput
screening, in which hundreds of thousands
of molecules could be tested to look for
“any particular activity to block a protein,
turn on a protein, or any other pharmacological activity,” said Dr. Olson. In
1996, Aurora Biosciences in San Diego,
California “had the technology in a niche
market,” whereby they “specialized in
building florescent-based technology
for screening and identifying drugs that
could affect ion channels, sodium chloride
and calcium channels.” According to Dr.
Olson, Aurora formed an agreement with
the Cystic Fibrosis Foundation to focus on
CF. Through this pilot program, Aurora
found molecules that appeared to “turn on
or restore the CFTR function.” In 2001,
Vertex Pharmaceuticals purchased Aurora.
The research challenge, shared Dr. Olson,
was that, “Most enzymes block or stop a
protein from doing its function. We were
trying to make the protein come to life and
function.” In 2004, VX-770 showed the
potential to do this, and in 2005, the VX-
Based on the results of this, VX-770 was
advanced to phase 2 trials. Dr. Olson
noted that based on the small number of
adult patients with the G551D mutation,
it was a challenge to find twenty subjects for the study. The main outcome of
the trial was to measure changes in the
sweat chloride. Dr. Olson shared, “One
of the more emotional times of my whole
career was when two physicians called
me into the office to show me the data
from the study with the patients.” The
data showed dramatic drops in sweat
chloride. “We knew we were on the right
–Eric Olson, Ph.D.
12
track, and that it was possible. Spring of
2008 will forever live in my memory.”
Not only did the study mark an important
proof of concept, Dr. Olson said, but also,
“Proof of principle. It showed you could
give someone with CF a pill, and that this
drug could get into the body and restore
the function of the protein.”
Based on the promising results of the
phase 2 trials, Dr. Olson and his team at
Vertex worked simultaneously with the
FDA and European regulators to initiate a
pivotal phase 3 trial, which began in 2009.
When the first results were seen in February 2011, “the race was on,” to provide
all the necessary information together for
both the FDA and European regulators.
Said Dr. Olson, “It was a nerve-wracking
time. Never underestimate the amount
of work required to bring a product to
manufacture and to market. Whether for
1,000 people or a million, it requires the
same amount of work.” VX-770, renamed
Kalydeco, was approved by the FDA in
January 2012.
The work on Kalydeco is only a part of
Dr. Olson’s story. Another promising molecule, VX-809, had been discovered by
Vertex researchers and was being explored
as a “corrector,” to address patients with
the Delta F508 mutation. Delta F508 is a
class II mutation, which causes the CFTR
protein to misfold, and prevents it from
reaching the epithelial surface. Eighty
percent of people with CF have a class
II mutation. In an early study, patients
homozygous for Delta F508 were given
VX-770. While they did not have a significant clinical response, Dr. Olson noted
that the study “gave important information
for a combination approach.” He added,
“In June, 2011, we saw for the first time
that a corrector and potentiator could work
together to improve CFTR function.”
VX-809 - the corrector - helps move the
protein to the cell surface, while the potentiator, VX-770, helps the protein channel
to open and function. Dr. Olson noted that
he and his colleagues are currently, “in the
middle of dissecting that data.”
As for the future, Dr. Olson was very
enthusiastic. “Now that we know the
science that led to this, we think that this
same science can be applied to a much
Fall 2012
larger group of patients. We have another
drug in clinical development. The team in
San Diego is still screening, doing chemistry, and looking for even better molecules.
We are on a very strong scientific foundation, and someone will harvest that and
develop new therapies.”
While Dr. Olson provided insights from
the development side of Kalydeco,
Dr. Michael Boyle, as Director of the
Adult CF Center at Johns Hopkins Medical Center, was able to share his personal
perspective as both a principle investigator for the Vertex combination trial, and
a CF practitioner who witnesses firsthand
the effects of Kalydeco. Noting that, “Dr.
Olson is limited about what he can say,”
Dr. Boyle had more liberty to provide
encouraging details from the field.
“The most striking result from the phase
3 study, looking at the 48-week data,
was that the FEV1 of those treated with
Kalydeco improved by approximately
10% after two weeks, and continued to
show this significant difference throughout
the study,” said Dr. Boyle. “This has been
confirmed in a follow-up study, following patients for an additional two years.”
In addition to the improvements in lung
function, Kalydeco is, “correcting CFTR
throughout the body, making a difference
in some of the key clinical outcomes.”
Kalydeco’s impact on sweat chloride
levels, which so moved Dr. Olson in early
clinical trials, has held true in clinical
practice. Dr. Boyle shared that patients
treated with Kalydeco had their sweat
chloride levels drop from approximately
100 mmol to less than 60 mmol. This is
significant, in that 60 mmol is used as the
cutoff for cystic fibrosis diagnosis.
According to Dr. Boyle, adult patients
treated with Kalydeco had an average
weight gain of approximately 7 pounds,
and a 55% reduction in pulmonary exacerbations. Those taking Kalydeco consistently cited an improved quality
of life. A phase 3 study was conducted
with children aged 6 to 11 years old
with at least one G551D mutation. The
results from this study, said Dr. Boyle,
“were almost identical to the results
for adults.”
While the study results were resoundingly
positive, Dr. Boyle noted that Kalydeco’s
“real life application” was equally
encouraging. “People who were on the
study drug knew they felt better.” They
told Dr. Boyle that they noticed a “significant decrease in cough, and also increased
energy.” Many cited “a general sense of
well-being.”
Michael Boyle, M.D.
Dr. Boyle emphasized that those who
take Kalydeco must still adhere to their
previous medical regimen, including
respiratory therapy. Kalydeco “cannot
undo previous lung structural damage
that a patient already has.”
Noting that bronchiectasis and previous
scarring are irreversible, Dr. Boyle emphasized that Kalydeco, “does restore some
of the physiology that will help to prevent
future damage.” In the future, he added,
“maybe we will be able to use it with kids
who have not experienced lung damage,”
thus preserving their lung function.
CF pulmonologists have long stressed
the critical importance of doing what is
necessary to preserve lung function. With
the approval of Kalydeco, this advice is
resonating with Dr. Boyle’s patients – particularly with teens – because it represents
the potential for new treatments in the near
future.
In acknowledging that Kalydeco is only
approved for use by a small percentage
of CF patients, Dr. Boyle pondered who
else might benefit from the drug in the
future. The “low-hanging fruit,” according to Dr. Boyle, are those with other class
III mutations, as well as those with class
IV mutations, where the CFTR protein is
already at the surface.
Combination therapy holds great promise
for those who carry the Delta F508 mutation, as 87% of people with CF carry at
least a single copy, while approximately
50% are homozygous for the mutation. In
addition to the corrector VX-809, Vertex
is studying VX-661, which also helps
traffic CFTR up to the surface to help act
as a channel. A recent study of people
homozygous for the Delta F508 mutation included, “28 days of monotherapy
with VX-809 to get the protein to the
surface, followed by 28 days of combination therapy with VX-809 and Ivacaftor
(Kalydeco).” According to Dr. Boyle,
while the data is not published yet, top
line data indicated a “mean absolute
improvement of 6% in lung function.”
Due to the results, Vertex and clinical
investigators will advance to phase 3
trials. At the same time, VX-661 is in
phase 2 trials with 120 patients. Said
Dr. Boyle, “At the end of day, we spoke a
lot about Ivacaftor (Kalydeco), but there
is a lot of promise and potential with
VX-809 and VX-661 to help with trafficking, and hopefully to see the results that
we have seen with Ivacaftor.” Dr. Boyle
encouraged patients to talk with their
doctors, and to “Please look to see what
studies are ongoing if you are eligible, so
you are guaranteed the drug.”
In closing, Dr. Boyle noted that while
many questions have been answered,
there are others to consider, including: “What are the long-term effects of
Ivacaftor on CF individuals with G551D?
Can we protect younger patients’ lungs?
Will Ivacaftor be beneficial in other
classes of mutations with preserved CFTR
function? Will VX-809 or VX-661 in
combination with Ivacaftor be beneficial
in Delta F508 so as to help 87% of other
patients? Will we be able to develop other
strategies for those with a lack of CFTR
in class I mutations?”
The future holds promise for those living
with CF. As Dr. Olson noted, “This is
clearly not the end of a story – in fact,
we think we’re just at the beginning.”
13
Fall 2012
E
Life Lessons and More for a
CFRI Intern
By Kevin Lin
xcuse me? I sat in silence. Frozen.
How could one question provoke
so deeply? The voices in the room
began to fade into the sounds of the air
conditioning. I became fixated on that
one question.
second day of the retreat at a rap session.
The conversation at the time was geared
more towards people with CF, so I wasn’t
concentrating fully. As I sat there, caught
off guard, someone asked: “What is your
mission statement in life?”
I didn’t know. I didn’t know and it scared
me. Here I was, 17 years old, a senior in
high school and off to college soon, not
knowing what I wanted. I thought about
this question in the shower, at my desk at
CFRI, and during car rides. Even now, I
don’t know.
Intern Kevin Lin with Volunteer Joyce Chang
Let’s back up. Allow me to introduce
myself. My name is Kevin Lin and last
summer I worked at CFRI for five weeks
as a marketing intern, before my senior
year of high school. At first, I did not
know what I was getting myself into. I
expected to be cast off in an office corner.
But I was wrong. I was taken in by the
staff as one of their own, able to take initiative on office projects while learning
about the inner workings of a non-profit.
At the CFRI Conference, it was rewarding to see that all my work, including the
name badges, the brochure covers, the
handouts, and the press releases I wrote
to promote this event had their “prime
time” in the spotlight.
After the conference ended, I went
straight into the Teen and Adult Retreat.
The experience was eye-opening. There
was no non-CF/CF tension at all, as I had
initially expected. From breath-concentrated yoga, to rocking out U-Jam style,
to having engrossing lunch conversations, to participating in enlightening
group talks, I was welcomed as one of
the group. I was also able to participate in
the daily rap sessions - group gatherings
where we vented, talked, and explored
certain issues relating to CF.
Which leads me back to my fixation
on the question which sent off flashing red panic alarms for me. It was the
14
But what I do know is that by the end of my
internship, I learned valuable life lessons
and a bit more about myself. By the end of
my time at CFRI, besides figuring out what
PFT’s measured and what the FEV1 test
was, I learned to appreciate even the smallest of loves, to go out and try new experiences, and to do what makes me happy.
Looking back years from now, I won’t
remember all the name tags I created or the
raffle prize I won. But I will remember the
lives I’ve touched and the knowledge that
I have a supportive community to fall back
on. Thank you Carroll, David, JoAnn and
Mary. Thank you Retreaters. Thank you CF
Community for letting me catch a glimpse
of my life’s mission statement.
For information about internships at
CFRI, please contact Mary Convento at
650.404.9975 or [email protected].
Surf’s Up!
Wine for a Cure
Hosts Elegant
Reception
L
ast May, Wine for a Cure held an
outstanding benefit for CFRI, which
included a wine reception hosted
by the Winemaker’s PourHouse, featuring
local vintners from Livermore, California.
Music by singer-songwriter Chris LeBel set
the tone for an intimate event. NBC Bay
Area reporter Bob Redell, Master of
Ceremony for the afternoon, recognized
Tara Goodearly and others with cystic
fibrosis (CF) as heroes facing the challenge
of this disease.
Carroll Jenkins was presented with the
2012 Caregiver of the Year Award for her
dedication to the CF community and for
ten years of service as Executive Director
at CFRI.
The reception was followed by a screening
of the award-winning film, The Power of
Two at Cinema West, and a special Q&A
opportunity with the cast, crew and other
special guests.
Thanks to Diana Heppe, Robin Modlin
and wonderful volunteers, over $10,000
was raised for CFRI. A special thanks to:
The Pleasanton Lions Club, Doug and Jan
Heppe, and all of the generous sponsors
who made this possible.
On September 29th, a wonderful
benefit dinner and auction was
hosted by “Friends Cure CF” at the
Best Western Seacliff Inn in Aptos,
California. Inspired by the Altano
family, funds were raised for the
Living Breath Foundation and CFRI.
Generous donations supported the
cause: to impact the critical needs of
CF patients, to help them “breathe
easy.” Thanks to the Seacliff Inn for
their hospitality, to the Altanos and
to all the volunteers who created this
lovely evening.
Tara Goodearly and Bob Redell
Fall 2012
CFRI Retreat:
An Unforgettable Experience
T
By Robert Cumming
his year was my
first time going
to CFRI’s Teen
and Adult Retreat.
It was an experience
I will never forget.
From the people whom
I met, to good times
shared, that one week
was like nothing I had Robert Cumming
ever experienced.
I had never done anything involving the CF
community before, except for Great Strides.
I always thought, “I have CF and I can
deal with it in my own way.” However, the
Retreat isn’t just a place to get information
and advice from your peers on how to work
with health care providers, or to learn
how to deal with what’s going on; it’s so
much more! It is a place to be understood,
THANK YOU TO THE
SPONSORS OF CFRI’S
RETREAT!
Abbott Laboratories
Boomer Esiason Foundation
Foundation Care Pharmacy
Gilead Sciences, Inc.
Genentech, Inc.
Kelly Colgan Golf Classic
Lockheed Martin Employees’
Foundation
Maggie’s Miracle Makers Sheehan Family
Vertex Pharmaceuticals
a place to get to know others going
through the same hardships you’ve
been through, and to understand what
may lie ahead. This event is more than
just a get-together of people going
through the same thing. For that one
week, it quickly becomes like a family
and a home. The hardest thing about attending the retreat was having to leave.
I can’t wait for next year!
THANK YOU
TO THE SPONSORS
AND EXHIBITORS OF
CFRI’S 25TH NATIONAL
CF FAMILY EDUCATION
CONFERENCE!
The conference would not be possible
without their generous support.
SUSTAINING SPONSORS
Genentech, Inc.
Novartis Pharmaceuticals
Vertex Pharmaceuticals, Inc.
PLATINUM
Abbott Laboratories
Boomer Esiason Foundation
Gilead Sciences, Inc.
GOLD
Aptalis Pharma, Inc.
CF Services Pharmacy
Foundation Care
Hill-Rom
Patty and Gene Holmquist
SILVER
Cystic Fibrosis Pharmacy, Florida
Digestive Care, Inc.
Electromed, Inc.
Med Systems
RespirTech, Inc.
Swank Audio Visuals
SUPPORTERS
Altano Family
Mark Clarin
Brad Huntzinger and Kendal Hall
Peggy B. Jones
Manuel Naku
Nelson Biotechnologies, Inc.
PARI Respiratory Equipment, Inc.
Prodigy Press, Inc.
Sheehan Family
Sofitel San Francisco Bay
15
Fall 2012
CFRI Celebrates Aitken and Tillman
With Top Awards
E
By Bridget Barnes
ach year at the annual conference,
CFRI recognizes a top professional
and volunteer, to honor their extraordinary contributions to the cystic
fibrosis (CF) community. Nominations
are received from across the country, and
winners are selected by past recipients of
these awards.
This year’s 2012 Professional of the Year
Award was awarded to Dr. Moira Aitken,
an outstanding physician who is devoted
to the improvement of CF clinical outcomes and to the advancement of clinical
care in cystic fibrosis. She is currently
Professor of Medicine at the Division
of Pulmonary and Critical Care at the
University of Washington in Seattle, and
Director of their Adult CF program and
Pulmonary Clinic. Dr. Aitken graduated
from the Medical School at Edinburgh
University in Scotland and continued postgraduate training at Western General Hospital in Edinburgh, the Royal Infirmary in
Edinburgh and the University of Washington. Practicing since 1985, Dr. Aitken has
been the recipient of many honors during
her career.
Dr. Aitken established one of the first
adult CF centers in the United States at
the University of Washington, where she
continues to provide critical leadership of
Moira Aitken, M.D.
16
the Adult CF Clinic, as well as daily work
“in the trenches” of clinical care. She
actively supports the Adult CF program
within the hospital and maintains a positive, “can-do” attitude, always advocating
for more CF resources. Dr. Aitken’s clinic
offers 24-hour access to patients and she
has coordinated with many physicians
throughout the northwest to deliver the best
CF care close to the homes of patients.
Dr. Aitken has devoted a significant part of
her career to CF research, and as a member of the Royal College in Edinburgh, she
has published over 100 original research
papers. As a teacher, she is known for her
“ceaseless enthusiasm,” and she takes the
lead in training adult fellows in the care of
CF patients at the University of Washington. Dr. Aitken’s unique mix of qualities
– accessibility, skill, compassion, and
honesty – lead to significant bonds with
her patients. As a quintessential mentor,
brilliant scientist and compassionate clinician, Dr. Moira Aitken has all the ingredients of a great doctor.
The 2012 Dave Stuckert Memorial
Volunteer of the Year Award, named after
one of CFRI’s earliest presidents, was
awarded to Laura Tillman. Born in 1948
and not diagnosed with CF until age 47,
Tillman has been educating herself and
others since 1995 on how to best live a
full life with cystic fibrosis. She has been
director of the United States Adult Cystic
Fibrosis Association (USACFA) since
2003 and as their current President, leads
the field in sharing the voices of adults
with CF. Tillman writes a regular column
for USACFA’s quarterly publication, CF
Roundtable, in which she shares vital
information gathered from the internet and
other sources on a myriad of topics.
Tillman’s involvement with the CF
community includes serving many
organizations, including the Michigan
Pulmonary Disease Community, Inc.,
and the University of Michigan Medical
School Mentoring Program for CF doctors. She has participated in podcasts, panel
Laura Tillman
discussions and webcasts, sharing her CF
experience with others. She is also a highly
valued volunteer for CFRI. Over the years
as a Conference Committee member, Laura
Tillman has given her time and expertise
in helping with planning, participating on
panels, facilitating support groups, encouraging attendance and volunteering in
the hospitality area. She is also a regular
columnist for CFRInews, and synthesizes
information from a variety of sources to
examine in depth a particular topic regarding CF. Laura Tillman is a CF community
treasure: always willing to assist others
and share her positive outlook.
CFRI applauds these two remarkable
women, who do so much to enrich and
support the CF community.
Send in Your Nomination!
Seize the opportunity to recognize the
efforts of someone who makes a real
difference in the world of CF today.
To make a nomination for the
CFRI Professional or
Volunteer of the Year
contact the CFRI office for
2013 guidelines:
[email protected]
Fall 2012
CFRI Members Attend the 2012 Transplant
Games of America, Returning Victorious
T
By Anabel Stenzel
eam Northern California returned
victorious from the 2012 Transplant Games of America, held this
year in Grand Rapids, Michigan from July
27 to July 31. Twenty-one athletes, ages
17 to 65 – all of whom have had organ
transplants – competed among 1000-plus
athletes from over 38 teams nationwide in
13 sports. “Team Nor Cal” brought home
57 medals, including 36 gold, 13 silver,
and 8 bronze, in swimming, track and
field, tennis, table tennis, badminton
and cycling, ranking fourth in the nation.
In addition, the women’s relay teams in
track and field, and swimming, won gold
in four events.
Thirteen family members of organ donors
also joined Team Northern California. All
of these families lost loved ones and chose
to give life to others at a time of tragedy.
Four athletes were adults with cystic
fibrosis (CF) who have received lung
transplants and are members of the “CFRI
family.” They included Tom Martin, Anna
Modlin, Isabel Stenzel-Byrnes and myself.
Together, we brought home 21 of the
team’s medals. As a CFRI Board member
who has attended six Transplant Games,
I served as this year’s manager for Team
Northern California, and won 4 gold, 3 silver, and 2 bronze medals in track and field
and swimming. Much like our CF community gatherings, the Transplant Games
are like a family reunion, a love fest.
The event is a celebration of health, yet
inspires a mix of grief, loss, love and hope
as we celebrate the miracle of transplant,
while mourning the loss of our donors. At
the Games, we push our bodies to the max,
as if our donors are watching.
The Transplant Games are part summer
camp, part carnival, and part educational
conference mixed with friendly sport competition and encouragement. We celebrate
all the gifts that transplant offers: health,
the ability to achieve new levels of fitness,
fellowship, learning from others around
the country, the generosity of sponsors,
and the commitment and leadership of the
medical community.
Says Tom Martin, “This was my third time
at the Transplant Games and I’m always
inspired by the enthusiasm and friendly
competition.” He adds, “It’s a great privilege and honor that I’m able to compete.
This year, I finally won the gold in the
100m dash (track and field), all thanks to my
teammates’ support and encouragement.”
Twenty months ago, Anna Modlin
received a double lung transplant. This
year she attended the Transplant Games
for the first time, winning five gold medals in swimming. Modlin reflects, “These
were my first Games since my transplant.
They gave me a sense of accomplishment
and a level of physical fitness I haven’t
had in many years. It was a transformative experience and has encouraged me
to get more involved and to work harder
spreading organ donation awareness and
to continue my fitness goals.”
These were the fifth Transplant Games
for Isabel Stenzel-Byrnes, who received a
double lung transplant in 2004, and who
brought home six gold medals in swimming. “The most rewarding experience
of the Games for me was participating in
the 4 x 50 women’s medley and the 4 x 50
women’s free relay swim event with Anna
Modlin, my sister Anabel, and another
teammate. After sharing the challenging
journey of cystic fibrosis with the Modlin
family for over 20 years, what a celebration it was to be healthy enough to swim
together,” explains Stenzel-Byrnes, who
Anabel Stenzel, Anna Modlin, Isabel Stenzel-Byrnes
Tom Martin
is 40 years old. “The Transplant Games of
America is an extraordinary, life-affirming
event that provides indescribable hope. To
see an entire generation of people with CF
living 10, 15, 20 years post-double lung
transplant makes me believe in a long and
happy future!”
The Transplant Games of America is a
biannual event that raises critical public
awareness about the life-restoring impact
of organ donation, and the immense need
for the public to register as organ donors
so that more lives can be saved.
Team Northern California is grateful for
the support of many sponsors, including Genentech, Inc., Stanford Hospital &
Clinics, the California Transplant Donor
Network, University of California, San
Francisco Transplant Programs, XDX Inc.,
LifeStars Jewelry, Black Diamond Pavers
and Landscapers, Blood Centers of the
Pacific, and the San Francisco Bay Area
Transplant Recipient International Organization (TRIO). For more information
or to join Team Northern California in
2014, visit: www.teamnorcal.org or
find your local team at www.transplantgamesofamerica.org. To register to
be an organ donor, please visit:
www.donatelifeamerica.net.
17
Fall 2012
ADULT CARE (continued from page 5)
CF receive the best possible care. Dr.
Boyle studied both the top ten CF centers
(based on their pulmonary and nutritional
outcomes), and low performing centers as
well. He developed a comprehensive survey to capture the details of each center’s
clinical practice and collected data by
visiting the centers and conducting interviews. Dr. Boyle found that centers and
patients with outstanding outcomes shared
the following practices.
• Send the patient home from his or her
clinic visit with a care plan, detailing
recommendations for airway clearance,
nutrition, pulmonary medications and
diabetes, if appropriate.
• Recommend a home spirometry
device to measure FEV1 daily to keep
track of trends and identify exacerbations before they need treatment.
• Maximize use of time at clinic visits.
• Maintain an aggressive attitude
toward treatment, treat small declines,
and do not hesitate to use antibiotics.
• Have a pre-clinic meeting with the
“team” prior to patient’s appointment.
• Don’t allow long stretches of missed
clinic visits or medications.
• Encourage the patient to prepare
for clinic as well, with a list of key
concerns and questions about ways to
improve his or her care.
• “Make it personal,” by working
closely with the patient to overcome
obstacles to adherence, such as cost,
anxiety, depression, fear and embarrassment.
• Involve patients in their care at an
early age by regularly giving them
feedback; a visual image is very
effective, such as a graph of their
FEV1 results, so they can “literally
see” how they’re doing.
• Make sure centers provide, and
patients understand, their health data,
such as FEV1 trends, weight and Body
Mass Index (BMI), microbiology (cultures), key labs and radiology (x-ray).
• Schedule Chest CT “interventions.”
Dr. Boyle showed a picture of the lungs
of a 22 year old adult with 92% predicted
FEV1. “It actually showed damage,
which can inspire a person to do treatments. In fact, I had one patient put it
on his fridge for visual feedback.”
• Encourage honesty between doctor
and patient. “With adults,” Boyle noted,
“anxiety and depression are big barriers.”
But how does one best prepare a child
with CF to be a successful adult with CF?
A successful transition from childhood to
adulthood depends on learning healthy
habits at an early age. “Seven of the top
ten adult CF centers grew out of the top ten
pediatric centers, demonstrating that what
we do during the pediatric years can set
the trajectory for adulthood,” Dr. Boyle
explained, emphasizing that the transition
from being a child to an adult starts at a
young age. According to the data collected
for the survey, preparing for successful
adult care employs the following principles:
“Transition, not transfer; start early; and,
parental guidance is essential, but it is also
absolutely essential that you not help your
child with everything.” Quoting the famous
coach John Wooden, Dr. Boyle said, “The
worst thing you can do for someone you
love is to do that which they could and
should do for themselves.” The ideal
transition is, “less parent, more child.”
Specific goals for successful transition
were established for each age group in
two-year increments ranging from 12 to
21, with increasing levels of responsibility as the patient gets older. For example,
“Naming your medications and reasons
for taking them,” is a goal for a 12 year
old, whereas “Describing choices about
smoking and drinking and their effect
on health in CF,” is suggested for an 18
year old. At 21, the goal is for the patient
to manage his or her care, and handle
everything from scheduling appointments
to being aware of details about insurance
and discussing strategies for future coverage with their caregivers. Patients living
with CF need to “develop a sense of selfresponsibility, not perfection,” Dr. Boyle
explained, and it is important for parents
to remember, “It is not only your child
who is transitioning, you are as well.”
In concluding, Dr. Boyle reiterated,
“What we do makes a difference. It’s not
all genetics. Partner with your caregivers
to assure you receive the best possible
care. And developing strategies towards
self-responsibility, not perfection, helps
young people with CF become independent and healthy adults.”
Teeing Off for CFRI at Beautiful Pasatiempo
S
cott Hoyt, the father of two daughters
with cystic fibrosis, hosted CFRI’s
28th Annual Golf Tournament at
Pasatiempo Golf Club, a USA “Top 100”
course in Santa Cruz, CA. A beautiful and
challenging course!
Scott Hoyt, General Manager at Pasatiempo
18
Thanks to volunteers and sponsors, and all
who made the day special. Next year’s
CFRI event will be on August 5, 2013.
Hope to see you there!
CFRI Supporters: Sarah Bauer, Adam Garlow,
Pat Capwell and Jarvis Roanhaus
Fall 2012
Probiotics for Cystic Fibrosis
P
By Laura Tillman
robiotic organisms are live microorganisms (yeast or bacteria) that,
when ingested in sufficient quantities, provide health benefits for the person
consuming them. Most probiotics are similar to the bacteria that are found naturally
in the gut. They prevent colonization, cell
binding and invasion by disease causing
organisms; they have direct antimicrobial
activity; and they exert a controlling influence on the host immune response. The
strongest evidence for the clinical effectiveness of probiotics has been in their use
for the prevention of symptoms of lactose
intolerance, treatment of acute diarrhea,
reduction of antibiotic-associated gastrointestinal side effects and the prevention
and treatment of allergy manifestations.
Research has also suggested that probiotics improve digestive function, improve
tolerance to lactose, decrease Helicobacter
pylori colonization of the stomach and
manage relapse of some inflammatory
bowel conditions.
In CF patients, the antibiotics that are taken
to kill the bacteria found in the lungs also
kill the bacteria and yeast that are normally
found in the gut. In many patients this can lead to diarrhea – specifically called
antibiotic associated diarrhea (AAD). The
two most common probiotics used in CF
patients are Lactobacillus species and
Saccharomyces boulardii. The University
of Maryland and their Center for Integrative Medicine recommend a probiotic
supplement (containing Lactobacillus
acidophilus), 5 - 10 billion CFUs (colony
forming units) a day, for maintenance of
gastrointestinal and immune health in CF.
The benefits of probiotics in CF patients
are shown in the following research:
Improvement of Intestinal Function
in Cystic Fibrosis Patients Using
Probiotics. Infante P. D.; Redecillas F.S.;
Torrent V. A.; et al. An Pediatr (Barc).
2008 Dec;69(6):501-505.
In some cases, cystic fibrosis may include
intestinal inflammation and bacterial
overgrowth. The authors concluded that
probiotics improved not only clinical but
also biochemical intestinal function in
cystic fibrosis patients.
http://tinyurl.com/boczysj
Effect of Lactobacillus GG Supplementation on Pulmonary Exacerbations
in Patients with Cystic Fibrosis:
a Pilot Study.
Bruzzese E.; Raia V.; Spagnuolo M.I.;
et al. Clin Nutr. 2007;26:322-328.
The researchers looked at how Lactobacillus GG (LGG) affects the lungs of CF
patients. They found that cystic fibrosis
patients who took LGG regularly had
fewer bouts with respiratory infections
than those that didn’t take LGG.
http://tinyurl.com/d3rua7n
Intestinal Inflammation is a Frequent
Feature of Cystic Fibrosis and is Reduced
by Probiotic Administration.
Bruzzese E.; Raia V.; Gaudiello G.; et al.
A. Aliment Pharmacol Ther. 2004;20:813819. The researchers looked at the benefits
to the intestines in this study. They found
that cystic fibrosis patients who take
Lactobacillus GG may have a reduction
in the intestinal inflammation that often
causes them pain.
http://tinyurl.com/cwz322c
Probiotic Supplementation Affects
Pulmonary Exacerbations in Patients
with Cystic Fibrosis: a Pilot Study.
Weiss B.;Bujanover Y.; Yahav Y.; et al.
Pediatr Pulmonol. 2010 Jun;45(6):536540.The authors found that probiotics
reduce pulmonary exacerbation rates in
patients with CF and that probiotics may
have a preventive potential for pulmonary
deterioration in CF patients.
http://tinyurl.com/btyz9xd
Probiotic Post-Transplant:
Important Warning
For transplant patients, both the Optic
Probiotics website and the Livestrong.
com website state that probiotics are not
recommended for individuals who are
severely immunosuppressed. Imunosuppressed patients do not have the ability
to mount an appropriate response to any
microbe with which they come in contact.
Microbes, even those that are normally
considered beneficial, can sometimes cross
the gut barrier and grow in the blood or
in the internal organs where the nutrients
are high and the competition for nutrients
is low. Growth in these areas can cause a
systemic infection. Also, individuals on
steroids are at increased risk of absorption
of probiotics into the bloodstream, causing
serious systemic infections. Antibiotic
resistance is another potential risk with
probiotic use.
Investigation of Probiotic Use
Among Inpatients at an Academic
Medical Center.
Jacques Simkins, M.D., Anna Kaltsas,
M.D., Brian P. Currie, M.D., MPH;
Presentation given at the Fifth Decennial
International Conference on HealthcareAssociated Infections; March 19, 2010.
Probiotic use has become very common;
related infections have been described in
immunosuppressed patients and those
with impaired intestinal integrity. Certain
probiotic package inserts now contain
warnings regarding their use in such
patients. Probiotic use was common in
patients with moderate to severe immunosuppression and in patients with impaired
intestinal immunity. Even though the
incidence of related bloodstream infections was low, these cases could have
been prevented.
http://tinyurl.com/d3nxnc7
Lactobacillus Probiotic Use in Cardiothoracic Transplant Recipients: a Link
to Invasive Lactobacillus Infection?
Luong M.L.; Sareyyupoglu B.; Nguyen
M.H.; et al. Transpl Infect Dis. 2010
Dec;12(6):561-564.
Organisms contained in probiotics are generally regarded as non-pathogenic and safe
to administer. The authors report a case of
pus accumulation caused by Lactobacillus in a human immunodeficiency virusinfected lung transplant recipient receiving a probiotic containing Lactobacillus
rhamnosus GG. The article compares the
incidence of Lactobacillus infections in
heart and lung transplant recipients at the
authors’ institution before and after the
(continued on page 22)
19
Chelsa Aboud
Connor Acheson
Gianna Altano
Altano Family
Ryan Anderson
Sadie Anderson
Hatsuko Arima
Jessica Arvidson
Patrick Aspinall
Kyle Baker
Haleigh Baker
Justin Balsley
Lucy Barnes
Bridget Barnes
Nick Barnes
Joseph Batchelder
Batchelder Family
Baugh Family
Evelyn Baughman
Maggie-Faye Bendz
Richard Bennett
Brett Bennett
Amanda Bergman
Allison Best
Aidan Biggar
Oliver Biggar
Rebecca Boyer
Monica Brown
Linda Burks
Brian Burks
Kevin Burleigh
Jane Burroni
Kyle Butler
Andrew Byrnes
John Cameron
Celia Canion
Andrew Carl
Justin Carnie
Tiffany Christensen
Barbara Christie
John Christie
Eva Clayton
Alyssa Collins
Lauren Colonna
Cameron Cornell
Cornell Family
Barbara Curry
Ashley Davila
Olivia Davis
Gordon DeVore
Rose DeVore
Felix Di Fonzo
Jason Dolan
Dylan Dunn
20
In
Honor of
Tess Dunn
Heather Edwards
Maxine Eggerth
Grace Ehrie
Elconin-Goldberg Family
Elyse Elconin-Goldberg
Daniel Ellett
Hayden Ellett
Tom Evans
Kristin Favero Konvolinka
Billy Federal
Alanah Fink
Jarrod Fischero
Victoria & Oscar Flamenco
Kathleen Flynn
Flynn-Wakefield Family
Ryan Foster
Joseph Fraker
Jacob Fraker
Jessica Fredrick
Emily Fredrick
Trevor Frisbee
Natasha Gaziano
Mark Gerow
Jenise Giuliano
Larissa Giuliano
Justin Goldman
Antonio Gonzalez
Tara Goodearly
Jen Goodwin
Emily Gorsky
Elizabeth Gougar
Beverly Goulette
Barbara Greenberg
Gianna Gutierrez-Serrato
Stephanie Halling
Julianna Harding
Tanner Harvill
Arieona Haskins
Marilyn Haupert
Christian Heavner
Tyler Heavner
Anthony Hidalgo
Shawn Hidy
Susan Hoffman
Jeremiah Holdaway
Joshua Holdaway
Courtney Hollis
Nicholas Hollis
Vincent Holmquist
Anne Houston
Erinn Hoyt
Kristen Hoyt
Clark Huddleston
Renee James
Steve Jenkins
Lindsey Jensen
Barbara Jensen
Edwin Johnson
Meghan Johnson
Peggy Jones
Laine Jones
Michelle Jones
Alex Karwowski
Franny Kiles
Edward Kinney
Eleanor Kolchin
Jason Konkel
Santosh Krishnan
Steven Kusalo
Sally Kusalo
Kaitlynn Lackey
Stacey Lawn
Kody Lawrence
Barbara Lenssen
Alyssa Linart
Michael Livingston
Ruth Livingston
Rose Logue
Alyson Lowery
Charlene Marshall
Eric Marten
David Martin
Claire McCabe
Tessa McCarthy
Lili McHugh
Rebecca McMullen
Beth McMullen
Carly McReynolds
Stacy Melle
Jackie Merrill
Linda Meyer
Fiona Mischel
Hannah Mitchell
Anna Modlin
Marcus Moses
Ann Mulligan
Philip Murphy
Jacqueline Murphy
Jessica Nett
Lindsey Nijmeh
Matthew Norman
Aly, Maddie and Killian O’Reilly
Dellene Ott
Dresden Page
Annette Palmer
Fall 2012
“In Honor of”
and “In Memory of”
Our “In Honor of” and “In Memory
of” pages provide the opportunity
to honor a person, family, or special
event or to remember a loved one.
If you want your donation to honor
or remember someone special, please
include the person’s name and address
with your donation.
At your request,
we will send an acknowledgement of
your gift to the person you designate.
Mail your contributions to:
CFRI,
2672 Bayshore Parkway,
Suite 520,
Mountain View, CA 94043
Contributions listed here were
received between April 16, 2012
and August 31, 2012.
Scott Parks
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Robinson Family
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In Memory of
Carol Adelman
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Fall 2012
Melvin Sachs
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Tom Walton
Sean Waltrip
Viola Wastell
Nicky Wastell
Joel Wastell
Shirley Wastell
Ken Wastell
Tara Weir
Hayley Wester
Tina Williamson-Crow
Kelly Wilson
21
Fall 2012
BEST OUTCOMES (continued from page 3)
drug concentrations at the site of infection,
and minimizes systemic exposure to the
drug. In Canada, tobramycin is available as
a powder and delivered through a portable
breath-actuated inhaler. Adult patients
favor this method as it can be done more
quickly than inhaled TOBI, has better
delivery, and is more convenient.
“Inflammation is tricky business in cystic
fibrosis,” according to Dr. Ratjen, noting
that it is an important immune response,
but can create a worsening cycle in the
lungs. What is the right balance between
infection and inflammation? “It’s much
easier to treat an inflamed joint than
an area where there is bacteria,” Dr.
Ratjen explained. “Ibuprofen is the only
approved anti-inflammatory for CF and is
not used much.” A 2004 study investigating
pulmozyme as an ancillary treatment for
airway inflammation found that those who
used pulmozyme had an indirect result of
clearing infected mucus from their airways,
reducing inflammation and preventing
infection. Azithromycin, an oral antibiotic
and anti-inflammatory drug, was also
studied in CF patients with mild disease.
Patients who took the drug had fewer
infections and less inflammation.
bial activity. In addition, for every mucosal H2O2 produced, DUOX also generates
an intracellular proton that needs to be
released or otherwise DUOX is blocked.
In other words, DUOX is pH sensitive
and is blocked by acidity. For DUOX to
operate properly, a release mechanism for
intracellular protons is required.
buffered airway pH is critical for normal
airway defenses.
In looking to the future and what is on the
research horizon, Dr. Ratjen emphasized,
“We need to develop multiple, parallel pipelines and not just a single approach. To solve
the CF puzzle, all pieces must fit together.”
RESEARCH (continued from page 1)
liquid in CF was controversial initially
(because it turned out to be very difficult
to measure) and it did not offer a clear
explanation for CF lung disease because
no defense functions were clearly affected
by pH changes.
The finding of a new defense factor in
the lung provided a major breakthrough.
Phagocytic white blood cells are the body’s
champions of bacterial killing, and we
reasoned that the lung epithelium might
use a similar mechanism. Christian
Schwarzer, then a CFRI-funded postdoctoral fellow, identified an NADPH oxidase
(now called DUOX) in lung epithelial cells
that was an isoform of the bactericidal
NADPH oxidase found in phagocytes. This
finding suggested that the lung epithelium kills bacteria just the same way as
phagocytes do. We found that DUOX is
an epithelial defense factor that generates
hydrogen peroxide (H2O2) in the airways,
which (in the presence of additional
factors) efficiently kills bacteria. Others
found that when DUOX is inactivated, the
airways completely lose their antimicro-
22
We investigated a number of known proton transporters and found that the airway
epithelium expresses a proton channel
(called HVCN1) that had previously been
described in phagocytes. Thus, the airway
epithelium expresses a defense mechanism
that is quite similar to the mechanism
found in phagocytes to kill microbes. In
phagocytes, a pH dependence of killing
has been noted experimentally but because
the blood pH is very well buffered, their
operation is not significantly limited by
pH. In contrast, the airway surface liquid
is extremely thin (1 microliter per square
centimeter), and its buffering power is
largely dependent on the bicarbonate that
is delivered into it by CFTR. Thus, our
recent findings suggest that a properly
The parallel operation of the CFTR
bicarbonate channel and the HVCN1 proton channel is intriguing as they determine
the final airway pH and support proper
DUOX activity. Currently, we are investigating the intimate relation between the
three factors, which we call the CFTRHVCN1-DUOX axis. All three factors
operate together as one antimicrobial
complex and we aim to identify the best
way to normalize its function in CF.
I wish to thank CFRI for its outstanding
contributions to CF research. CFRI provides leadership and maintains a vibrant
community of CF researchers.
PROBIOTICS (continued from page 19)
introduction of this probiotic, and discuss
the potential mechanism for Lactobacillus
within the probiotic to cause infections
and to spread.
http://tinyurl.com/cmu74nf
Side Effects of Probiotics.
Ningthoujam Sandhyarani. Buzzle.com.
Last updated: November 16, 2011.The
author states that according to medical
studies, there is a possibility that probiotics interact with immunosuppressive
medications, leading to life-threatening
conditions. He concludes that those who
are on immunosuppressive drugs should
avoid probiotic use.
http://tinyurl.com/cberxqn
Fall 2012
NUTRITION (continued from page 4)
of kidney stones, constipation and distal
intestinal obstruction syndrome (DIOS),
and the importance of early screening
for colon cancer. Kidney stones are more
common among people with CF than the
general population. Schindler explained
that there is often an absence of the intestinal bacteria Oxalobacter formigenes,
and that there are commonly low citrate
levels in the urine of those with CF. She
stressed that “there is an inverse relationship between calcium intake and kidney
stones, and that maintaining a high
fluid intake, having adequate calcium in
one’s diet, and possibly the use of citrate
supplementation or probiotics may help
to prevent kidney stones.”
Schindler discussed the difference
between DIOS and constipation. DIOS
may cause a complete obstruction of
the intestine, and often causes extreme
abdominal distention, vomiting and
excruciating pain. The use of oral
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GoLYTELY® is usually prescribed for
a partial obstruction, while a complete
obstruction usually requires GoLYTELY®
administered via a nasogastric tube, along
with a gastrografin enema. Schindler
stressed that anyone who suspects that
they have DIOS should immediately
call their CF center, as this is a medical
emergency unique to CF.
It is now understood that there is an
increased incidence of gastrointestinal
(GI) cancers for those with CF, particularly colon cancer. This risk is further
increased post-transplant. Schindler listed
the potential symptoms of colon cancer,
including “blood in the stools, abdominal
pain, weight loss, persistent constipation
and unexplained anemia.” She strongly
advocated for earlier GI cancer screening
for those with cystic fibrosis, noting that
at her CF center in Cleveland, “we start at
35 with colonoscopies.”
By following Schindler’s advice, people
with CF may improve their health, and
quality of life.
REFLECTION (continued from page 7)
the beautiful Sofitel. The hotel staff was
amazing, and once settled into my room, I
was eager to start my learning experience.
children. Panels and support groups underscored that no one in the CF community
is alone.
At the start of each day, we were
reminded of the CF cross infection guidelines. The hotel staff ensured that these
guidelines were followed by wearing
gloves, and serving food and drinks to
attendees with CF.
In conclusion, I am very happy I was able
to attend the conference. I walked away
knowing more about myself, and with new
friends and family. As a newcomer, I was
welcomed as though I had been there year
after year. CFRI put much effort into creating this event. After a very educational,
emotional and successful three days, I
look forward to attending next year, and
hope this becomes a tradition for my
family and me.
During the three days, I heard many
knowledgeable speakers. There were
also helpful support groups, including
a “newcomers” meeting. I met several
other cystic fibrosis patients, family and
friends; even scientists participated in
these groups.
Brian, Natalie (who has CF) and Jana.
In closing, Schindler reviewed her
“take home advice,” for those with
CF, which included working with a CF
center registered dietitian to achieve
nutrition goals. She stressed the importance of maintaining proper vitamin
levels, including A, B, D, E and K, and
encouraged patients to discuss probiotics
with their doctors. “Ensure adequate calcium and fluid intake to reduce the risk
of kidney stones.” Schindler encouraged
patients to call their CF center if they
experience abdominal pain, but stressed
that they should “not adjust the enzyme
dose if abdominal pain and constipation
are the only symptoms,” unless they have
consulted with the dietitian. Adults with
CF should also talk with their doctor’s
about early screening for colon cancer.
From the kickoff on Friday to the “Ask
the Experts” panel on Sunday afternoon, a
rich variety of information was presented.
Attendees were updated on the pipeline
of new drugs, in particular, the latest from
Vertex: Kalydeco. We had great presentations on fertility issues for men and
women with CF, and discussions about
hot topics in nutrition, airway clearance,
and anxiety for parents of newly diagnosed
Eric Olson, Ph.D., and Maria Fioccola
23
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In this issue...
Kalydeco, VX-809 and
VX-661 page 1
New Drugs in the
CF Pipeline
page 3
Best Practices in
Adult CF Care
page 5
PTSD and CF
page 10
Victory at 2012
Transplant Games
page 17
Probiotics and CF page 19
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